Argonaute2 is the catalytic engine of mammalian RNAi
Abstract
Gene silencing through RNA interference (RNAi) is carried out by RISC, the RNA-induced silencing complex. RISC contains two signature components, small interfering RNAs (siRNAs) and Argonaute family proteins. Here, we show that the multiple Argonaute proteins present in mammals are both biologically and biochemically distinct, with a single mammalian family member, Argonaute2, being responsible for messenger RNA cleavage activity. This protein is essential for mouse development, and cells lacking Argonaute2 are unable to mount an experimental response to siRNAs. Mutations within a cryptic ribonuclease H domain within Argonaute2, as identified by comparison with the structure of an archeal Argonaute protein, inactivate RISC. Thus, our evidence supports a model in which Argonaute contributes “Slicer” activity to RISC, providing the catalytic engine for RNAi.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
No change of Ago2 function has been reported due to fusion with an epitope tag.
“no change of Ago2 function has been reported due to fusion with an epitope tag.”
From Cell-Type-Based Analysis of MicroRNA Profiles in the Mouse Brain (2012) · cites this paper as Liu et al., 2004
Cites
Sarot, E., Payen-Groschêne, G., Bucheton, A., & Pélisson, A. (2004) · Genetics · doi:10.1534/genetics.166.3.1313 · Cited by 251 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Regulation of microRNA biogenesis
Ha, M., & Kim, V. N. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3838 · Cited by 5,462 · see citing works
Circular RNAs are abundant, conserved, and associated with ALU repeats
Jeck, W. R., Sorrentino, J. A., Wang, K., Slevin, M. K., Burd, C. E., Liu, J., Marzluff, W. F., & Sharpless, N. E. (2013) · RNA · doi:10.1261/rna.035667.112 · Cited by 4,388 · see citing works
Self-citationMammalian microRNAs predominantly act to decrease target mRNA levels
Guo, H., Ingolia, N. T., Weissman, J. S., & Bartel, D. P. (2010) · Nature · doi:10.1038/nature09267 · Cited by 3,886 · see citing works
Regulation of mRNA Translation and Stability by microRNAs
Fabian, M. R., Sonenberg, N., & Filipowicz, W. (2010) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060308-103103 · Cited by 3,214 · see citing works
The evolution of gene regulation by transcription factors and microRNAs
Chen, K., & Rajewsky, N. (2007) · Nature Reviews Genetics · doi:10.1038/nrg1990 · Cited by 1,547 · see citing works
MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies
Liu, J., Valencia-Sanchez, M. A., Hannon, G. J., & Parker, R. (2005) · Nature Cell Biology · doi:10.1038/ncb1274 · Cited by 1,234 · see citing works
Self-citationStrategies for silencing human disease using RNA interference
Kim, D. H., & Rossi, J. J. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2006 · Cited by 1,078 · see citing works
RNA-Guided RNA Cleavage by a CRISPR RNA-Cas Protein Complex
Hale, C. R., Zhao, P., Olson, S., Duff, M. O., Graveley, B. R., Wells, L., Terns, R. M., & Terns, M. P. (2009) · Cell · doi:10.1016/j.cell.2009.07.040 · Cited by 1,031 · see citing works
Crooke, S. T., Witztum, J. L., Bennett, C. F., & Baker, B. F. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.004 · Cited by 841 · see citing works
AU-rich-element-mediated upregulation of translation by FXR1 and Argonaute 2
Vasudevan, S., & Steitz, J. A. (2007) · Cell · doi:10.1016/j.cell.2007.01.038 · Cited by 656 · see citing works
DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration
Kaneko, H., Dridi, S., Tarallo, V., Gelfand, B. D., Fowler, B. J., Cho, W. G., Kleinman, M. E., Ponicsan, S. L., Hauswirth, W. W., Chiodo, V. A., et al. (2011) · Nature · doi:10.1038/nature09830 · Cited by 601 · see citing works
High-Resolution Analysis of Parent-of-Origin Allelic Expression in the Mouse Brain
Gregg, C., Zhang, J., Weissbourd, B., Luo, S., Schroth, G. P., Haig, D., & Dulac, C. (2010) · Science · doi:10.1126/science.1190830 · Cited by 591 · see citing works
Targeted protein degradation by PROTACs
Neklesa, T. K., Winkler, J. D., & Crews, C. M. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.027 · Cited by 599 · see citing works
Kawamata, T., & Tomari, Y. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.03.009 · Cited by 481 · see citing works
Most Caenorhabditis elegans microRNAs Are Individually Not Essential for Development or Viability
Miska, E. A., Alvarez-Saavedra, E., Abbott, A. L., Lau, N. C., Hellman, A. B., McGonagle, S. M., Bartel, D. P., Ambros, V. R., & Horvitz, H. R. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030215 · Cited by 484 · see citing works
“elegans and mouse development [67,76].”
Life of RISC: Formation, action, and degradation of RNA-induced silencing complex
Iwakawa, H.-O., & Tomari, Y. (2022) · Molecular Cell · doi:10.1016/j.molcel.2021.11.026 · Cited by 488 · see citing works
An Overview of Some Biopesticides and Their Importance in Plant Protection for Commercial Acceptance
Kumar, J., Ramlal, A., Mallick, D., & Mishra, V. (2021) · Plants · doi:10.3390/plants10061185 · Cited by 474 · see citing works
ATP-dependent human RISC assembly pathways
Yoda, M., Kawamata, T., Paroo, Z., Ye, X., Iwasaki, S., Liu, Q., & Tomari, Y. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1733 · Cited by 380 · see citing works
From guide to target: molecular insights into eukaryotic RNA-interference machinery
Ipsaro, J. J., & Joshua-Tor, L. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2931 · Cited by 281 · see citing works
Self-citationCell-Type-Based Analysis of MicroRNA Profiles in the Mouse Brain
He, M., Liu, Y., Wang, X., Zhang, M. Q., Hannon, G. J., & Huang, Z. J. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.010 · Cited by 277 · see citing works
Self-citationThe regulation of mRNA stability in mammalian cells: 2.0
Wu, X., & Brewer, G. (2012) · Gene · doi:10.1016/j.gene.2012.03.021 · Cited by 239 · see citing works
An RNA toolbox for cancer immunotherapy
Pastor, F., Berraondo, P., Etxeberria, I., Frederick, J., Sahin, U., Gilboa, E., & Melero, I. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.132 · Cited by 229 · see citing works
Human Argonaute 2 Has diverse reaction pathways on Target RNAs
Jo, M. H., Shin, S., Jung, S.-R., Kim, E., Song, J.-J., & Hohng, S. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.04.027 · Cited by 207 · see citing works
Self-citationGeneral Principals of miRNA Biogenesis and Regulation in the Brain
O'Carroll, D., & Schaefer, A. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.87 · Cited by 205 · see citing works
Reexamining assumptions about miRNA-guided gene silencing
Kilikevicius, A., Meister, G., & Corey, D. R. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkab1256 · Cited by 194 · see citing works
MicroRNAs in placental health and disease
Mouillet, J.-F., Ouyang, Y., Coyne, C. B., & Sadovsky, Y. (2015) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2015.05.057 · Cited by 195 · see citing works
Kundu, P., Fabian, M. R., Sonenberg, N., Bhattacharyya, S. N., & Filipowicz, W. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks148 · Cited by 180 · see citing works
Regulation of cell-type-specific transcriptomes by microRNA networks during human brain development
Nowakowski, T. J., Rani, N., Golkaram, M., Zhou, H. R., Alvarado, B., Huch, K., West, J. A., Leyrat, A., Pollen, A. A., Kriegstein, A. R., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0265-3 · Cited by 166 · see citing works
High-Throughput Analysis Reveals Rules for Target RNA Binding and Cleavage by AGO2
Becker, W. R., Ober-Reynolds, B., Jouravleva, K., Jolly, S. M., Zamore, P. D., & Greenleaf, W. J. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.06.012 · Cited by 161 · see citing works
Momin, M. Y., Gaddam, R. R., Kravitz, M., Gupta, A., & Vikram, A. (2021) · Cells · doi:10.3390/cells10113097 · Cited by 107 · see citing works
Detzer, A., Engel, C., Wünsche, W., & Sczakiel, G. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq1216 · Cited by 74 · see citing works
Xu, J., Chen, Q., Zen, K., Zhang, C., & Zhang, Q. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12057 · Cited by 61 · see citing works
Target-dependent biogenesis of cognate microRNAs in human cells
Bose, M., & Bhattacharyya, S. N. (2016) · Nature Communications · doi:10.1038/ncomms12200 · Cited by 38 · see citing works
What does genetics tell us about imprinting and the placenta connection?
Varmuza, S., & Miri, K. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1714-0 · Cited by 22 · see citing works
Wang, Y., Tu, M.-J., & Yu, A.-M. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1423416 · Cited by 21 · see citing works
- Authors
- Liu, J., Carmell, M. A., Rivas, F. V., Marsden, C. G., Thomson, J. M., Song, J.-J., Hammond, S. M., Joshua-Tor, L., & Hannon, G. J.
- Affiliations
- Cold Spring Harbor Laboratory, Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
- Venue
- Science
- Published
- 2004-09-03
- Volume
- 305
- Issue
- 5689
- Pages
- 1437-1441
- ISSN
- 0036-8075
- 1095-9203
- Cited by
- 2,353
- References
- 1
- Language
- en
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
